Key Signaling Pathways in the Cardiovascular System

  • Fábio TrindadeEmail author
  • Inês Falcão-Pires
  • Andreas Kavazis
  • Adelino Leite-Moreira
  • Daniel Moreira-Gonçalves
  • Rita Nogueira-FerreiraEmail author


The activity of the heart and vessels is permanently modulated in response to electrical, mechanical and chemical signals to maintain cardiovascular system homeostasis. Some effects are rapidly manifested (e.g. contraction after an electrical stimulus), while others are observed at long-term (e.g. hypertrophy resulting from gene expression modulation). In any case, an orchestrated set of events follows from receptor to intracellular messengers and effectors via complex signaling routes. These include neurohumoral signaling targeting G protein-coupled receptors (such as adrenaline, angiotensin II and endothelin-1 receptors), growth factor pathways initiated at tyrosine (including insulin, vascular endothelial growth factor and fibroblast growth factor) or serine/threonine kinase receptors (transforming growth factor-β) or even direct intracellular/nuclear pathways (triggered by calcium, nitric oxide or thyroid hormones). Herein, the signaling pathways taking place in cardiomyocytes, endothelial cells, vascular smooth muscle cells and fibroblasts, mainly involved in the regulation of cardiac contraction, vasorelaxation, mechanotransduction, cell survival and hypertrophy are described. Finally, the role of extracellular matrix in cardiac remodeling and fibrosis is reviewed.


Cardiomyocytes Contraction Fibrosis Hypertrophy Intracellular signaling Vascular cells 



Adenylate cyclase


A-kinase anchor protein


Activin receptor-like kinases

Ang II

Angiotensin II


Atrial natriuretic peptide


β-adrenergic receptors


B-type natriuretic peptide






Ca2+/CaM-dependent protein kinase II


Cyclic adenosine monophosphate


Cyclic guanosine monophosphate


cAMP-responsive element-binding protein




Excitation-contraction coupling


Extracellular matrix


Endothelial cells


Epidermal growth factor


Nitric oxide synthase, endothelial


Extracellular signal-regulated protein kinase




Endothelin receptor A


Endothelin receptor B


Excitation-transcription coupling


Focal adhesion kinase


Fibroblast growth factor


Fibroblast growth factor receptor


Forkhead box protein O


Guanylate cyclase


G protein-coupled receptors


Glycogen synthase kinase-3β


Heparin-binding EGF-like growth factor


Histone deacetylase


Hypoxia-inducible factor-1α


Insulin-like growth factor


Inositol 1,4,5-trisphosphate


Insulin receptor substrate


c-Jun N terminal kinase


Voltage-dependent L-type calcium channels


Myosin light chain


Myosin light chain kinase


Myosin light chain phosphatase


Matrix metalloproteinase


Myosin-binding protein C


Sodium/calcium exchanger


Nuclear factor of activated T-cells


Nuclear factor NF-kappa-B


Nitric oxide


Neuregulin 1


Platelet-derived growth factor


PDGF receptor


Phosphatidylinositol 3-kinase


Phosphatidylinositol 4,5-bisphosphate


Phosphatidylinositol 3,4,5-trisphosphate


Protein kinase A


Protein kinase C


Protein kinase G




Phospholipase C


Renin-angiotensin-aldosterone system


Ryanodine receptor


Sarcoplasmic/endoplasmic reticulum calcium ATPase


Sarcoplasmic reticulum


Signal transducer and activator of transcription






Transforming growth factor-β


Thyroid hormone


TH receptors


TGF-β receptors


Vascular endothelial growth factor


VEGF receptor


Vascular smooth muscle cells



Thanks are due to the Portuguese Foundation for Science and Technology (FCT), European Union, QREN, FEDER and COMPETE for the financial support for the UnIC (UID/IC/00051/2019), iBiMED (UIDB/04501/2020) and CIAFEL (UIDB/00617/2020) research units and the research projects DOCnet (NORTE-01-0145-FEDER-000003) and NETDIAMOND (POCI‐01‐0145‐FEDER‐016385) and the post-graduation student (grant number SFRH/BD/111633/2015 to F.T.).


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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Fábio Trindade
    • 1
    • 2
    Email author
  • Inês Falcão-Pires
    • 1
  • Andreas Kavazis
    • 3
  • Adelino Leite-Moreira
    • 1
    • 4
  • Daniel Moreira-Gonçalves
    • 1
    • 5
  • Rita Nogueira-Ferreira
    • 1
    Email author
  1. 1.Department of Surgery and PhysiologyCardiovascular R&D Center, Faculty of Medicine of the University of PortoPortoPortugal
  2. 2.Department of Medical Sciences, iBiMED–Institute of BiomedicineUniversity of AveiroAveiroPortugal
  3. 3.School of KinesiologyAuburn UniversityAuburnUSA
  4. 4.Department of Cardiothoracic SurgeryCentro Hospitalar Universitário São JoãoPortoPortugal
  5. 5.Faculty of Sport, CIAFELUniversity of PortoPortoPortugal

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